Wnt/ß-catenin pathway is a key signaling pathway to trastuzumab resistance in gastric cancer cells.

BACKGROUND: Trastuzumab is the only approved target agent for the first-line treatment of human epidermal growth factor receptor-2 (HER-2) positive gastric cancer; however, trastuzumab resistance is a major problem in clinical practice. To comprehend the mechanism of trastuzumab resistance, we focused on the Wnt/ß-catenin signaling pathway and its influence on the phenotypes and behavior of trastuzumab-resistant gastric cancer cells. METHODS: Trastuzumab-resistant NCI-N87R cells were established in vitro from the human gastric cancer cell line NCI-N87 by dose-escalating repeated trastuzumab treatment. We investigated the phenotypes of NCI-N87R cells, including Wnt signaling pathway activity. Gastric cancer organoid cells were incubated with complete medium and Wnt3a-depletion medium, and their resistance to trastuzumab was compared. RESULTS: NCI-N87R exhibited stemness and epithelial-mesenchymal transition (EMT)-like phenotypes, along with decreased levels of the epithelial marker E-cadherin and increased levels of the mesenchymal markers Vimentin and Snail along with an increased Wnt signaling pathway activity. When gastric cancer cells were incubated in Wnt3a-conditioned medium. Wnt signaling pathway activity and resistance to trastuzumab increased. Gastric cancer patient-derived organoids incubated in Wnt3a-depletion medium were more susceptible to dose-dependent inhibition of cell viability by trastuzumab than those incubated in complete medium. CONCLUSIONS: Trastuzumab-resistant gastric cancer cells exhibited EMT-like phenotype, and trastuzumab resistance was promoted by the Wnt/ß-catenin signaling pathway. The Wnt/ß-catenin pathway is a key signaling pathway for trastuzumab resistance in gastric cancer cells.

Nomogram for pre-procedural prediction of non-curative endoscopic resection in patients with early gastric cancer.

BACKGROUND: Non-curative resection (non-CR) after endoscopic submucosal dissection (ESD) requires additional surgery due to the possibility of lymph node metastasis (LNM). Therefore, it is important to accurately predict the risk of non-CR to avoid unnecessary preoperative procedures. Thus, we aimed to develop and verify a nomogram to predict the risk of non-CR prior to ESD. METHODS: Patients who underwent ESD for early gastric cancer (EGC) were divided into CR and non-CR groups based on the present ESD criteria. The pre-procedural factors, such as endoscopic features, radiologic findings, and pathology of the lesion, were compared between the groups to identify the risk factors associated with non-CR. A nomogram was developed using multivariate analysis, and its predictive value was assessed using an external validation group. RESULTS: Among 824 patients, 682 were curative (82.7%) and 142 were non-curative (17.3%). By comparing two groups, endoscopic features including redness, whitish mucosal change, fold convergence, and large lesion size; histologic features such as moderately or poorly differentiated or signet ring cell carcinoma; and abnormal CT findings including non-specific lymph node enlargement and fold thickening were identified as significant predictors of non-CR. The nomogram was developed based on these predictors and showed good predictive performance in the external validation, with an area under the curve of 0.87. CONCLUSIONS: We developed a nomogram to predict the risk of non-CR prior to ESD. These predictive factors in addition to the existing ESD criteria can help provide the best treatment option for patients with EGC.

Association between triglyceride-glucose index and gastric carcinogenesis: a health checkup cohort study.

BACKGROUND: We aimed to investigate the association between the triglyceride-glucose (TyG) index and gastric carcinogenesis, including precancerous conditions such as dysplasia, atrophic gastritis, and intestinal metaplasia. METHODS: Patients who received an upper endoscopic assessment at a medical center were included. The enrolled patients were divided into four categories according to their TyG index quartile (Q). To evaluate the relationship between increase of TyG index and gastric cancer, we analyzed the patients who received a health checkup twice. Moreover, receiver-operating characteristic curve analysis was used to establish cut-off value of the TyG index for gastric cancer. RESULTS: Of 127,564 enrolled patients, 43,525 (34.1%) and 186 (0.1%) were diagnosed with precancerous conditions and gastric cancer, respectively. The odds ratios (ORs) of precancerous conditions given TyG index progressively increased across quartiles: using Q1 as the reference: Q2 (OR = 1.403, P < 0.001), Q3 (OR = 1.646, P < 0.001), and Q4 (OR = 1.656, P < 0.001). The ORs of gastric cancer also increased according to the quartiles: Q2 (OR = 1.619, P = 0.045), Q3 (OR = 2.180, P = 0.004), and Q4 (OR = 2.363, P = 0.001). Moreover, the increase in TyG index between baseline and follow-up tests was more significant in gastric cancer group than in control group (P = 0.001). The optimal cut-off value for predicting gastric cancer was 9.73. CONCLUSIONS: The TyG index may be a novel predictive biomarker for gastric carcinogenesis. Notably, increase in the TyG index is significantly associated with gastric cancer.

Comparison of long-term outcomes of endoscopic submucosal dissection and surgery for undifferentiated-type early gastric cancer meeting the expanded criteria: a systematic review and meta-analysis.

BACKGROUND: There have been concerns over the long-term outcomes of endoscopic submucosal dissection (ESD) for undifferentiated-type early gastric cancer (UD EGC). We aimed to compare the long-term outcomes of ESD and surgery for patients with UD EGC. METHODS: We searched PubMed, Embase, and Cochrane Library databases through March 2021 to identify studies that compared the long-term outcomes of ESD and surgery for UD EGC meeting expanded criteria for curative resection. The risk of bias was assessed with the Cochrane tool for non-randomized studies. The risk ratio (RR) was estimated using a fixed-effect model. RESULTS: Overall, 1863 patients from five retrospective cohort studies, including 908 patients with propensity score matching (PSM), were eligible for meta-analysis. ESD was associated with inferior overall survival (OS) compared to surgery in the overall cohort (RR 2.11; 95% CI 1.26-3.55) but not in the PSM cohort (RR 1.18; 95% CI 0.60-2.32). In the PSM cohort, ESD had a lower disease-free survival (DFS) (RR 2.49; 95% CI 1.42-4.35) and higher recurrence (RR 12.61; 95% CI 3.43-46.37), gastric recurrence (RR 11.25; 95% CI 3.06-41.40), and extragastric recurrence (RR 4.23; 95% CI 0.47-37.93). Recurrence outcomes were similar between the overall and PSM cohorts. Disease-specific survival was not significantly different between the two groups in both the overall and PSM cohorts. CONCLUSION: Although OS after curative ESD for UD EGC was not different from that after surgery in the PSM cohort, DFS and recurrence were inferior after ESD. Limitations included a lack of randomized trials. Further prospective studies comparing the long-term outcomes of ESD and surgery for UD EGC are needed (PROSPERO CRD 42021237097).

Prediction model for curative endoscopic submucosal dissection of undifferentiated-type early gastric cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) is an effective treatment for early gastric cancer (EGC); however, its curative resection rate is low for undifferentiated-type EGC. We developed and externally validated a prediction model for curative ESD of undifferentiated-type EGC. METHODS: In this cross-sectional study, we included 448 patients who underwent ESD for undifferentiated-type EGC at 18 hospitals in Korea between 2005 and 2015 in the development cohort and 1342 patients who underwent surgery at two hospitals in the validation cohort. A prediction model was developed using the logistic regression model. RESULTS: Endoscopic tumor size 1-2 cm (odds ratio [OR], 2.40; 95% confidence interval [CI] 1.54-3.73), tumor size > 2 cm (OR, 14.00; 95% CI 6.81-28.77), and proximal tumor location from the lower to upper third of the stomach (OR, 1.45; 95% CI 1.03-2.04) were independent predictors of non-curative ESD. A six-score prediction model was developed by assigning points to endoscopic tumor size > 2 cm (five points), tumor size 1-2 cm (two points), upper third location (two points), and middle third location (one point). The rate of curative ESD ranged from 70.6% (score 0) to 11.6% (score 5) with an area under the receiver operating characteristic curve (AUC) of 0.720 (95% CI 0.673-0.766). The model also showed good performance in the validation cohort (AUC, 0.775; 95% CI 0.748-0.803). CONCLUSIONS: This six-score prediction model may help in predicting curative ESD and making informed decisions about the treatment selection between ESD and surgery for undifferentiated-type EGC.

Long-term outcomes of endoscopic resection followed by additional surgery after non-curative resection in undifferentiated-type early gastric cancer: a nationwide multi-center study.

BACKGROUND: Undifferentiated-type early gastric cancer (UD EGC) shows lower curative resection rates after endoscopic submucosal dissection (ESD). Additional surgery is recommended after non-curative resection. We evaluated the long-term outcomes of ESD followed by additional surgery after non-curative resection in UD EGC compared to those for surgery as initial treatment. METHODS: We reviewed 1139 UD EGC patients who underwent ESD at 18 hospitals and 1956 patients who underwent surgery at two hospitals between February 2005 and May 2015. We enrolled 636 patients with non-curative ESD and 1429 surgery subjects beyond the curative ESD criteria. Among them, 133 patients with additional surgery after ESD (ESD + OP group) and 252 patients without additional surgery (ESD-only group) were matched 1:1 using propensity scores to patients with surgery as initial treatment (surgery group). Overall survival (OS) and recurrence-free survival (RFS) were compared. RESULTS: Signet ring cell carcinoma and poorly differentiated adenocarcinoma (PDA) were observed in 939 and 1126 cases, respectively. OS was significantly longer in the surgery group than in the ESD + OP group, especially for PDA. However, RFS was shorter in the ESD-only group than those in the ESD + OP and surgery groups. RFS did not differ significantly between the ESD + OP and surgery groups. Compared to the surgery group, the ESD-only and ESD + OP groups had an overall hazard ratio for RFS of 3.58 (95% confidence interval 1.44-8.88) and 0.46 (0.10-2.20), respectively. CONCLUSIONS: ESD followed by additional surgery after non-curative resection showed comparable cancer-specific outcomes to initial surgery in UD EGC.

Consistency of Helicobacter pylori eradication rates of first-line concomitant and sequential therapies in Korea: A nationwide multicenter retrospective study for the last 10 years.

BACKGROUND: Eradication rate of standard triple therapy for H. pylori has declined to unacceptable level, and alternative regimens such as concomitant and sequential therapy have been introduced. We aimed to assess the consistency of eradication rates of concomitant and sequential therapies as for the first-line H. pylori eradication in Korea. METHODS: A nationwide multicenter retrospective study was conducted including 18 medical centers from January 2008 to December 2017. We included 3,800 adults who had test to confirm H. pylori eradication within 1 year after concomitant or sequential therapy. RESULTS: Concomitant and sequential therapy were prescribed for 2508 and 1292 patients, respectively. The overall eradication rate of concomitant therapy was significantly higher than that of sequential therapy (91.8% vs. 86.1%, p < .001). In time trend analysis, the eradication rates of concomitant therapy were 90.2%, 88.2%, 92.1%, 94.3%, 91.1%, and 93.4% for each year from 2012 to 2017 with an increasing trend (p = .0146), while those of ST showed no significant trend (p = .0873). Among 263 patients with second-line therapy, bismuth quadruple therapy showed significantly higher eradication rate than quinolone-based triple therapy (73.9% vs. 51.5% in ITT analysis, p = .001; 82.7% vs. 63.0% in PP analysis, p = .002). CONCLUSION: Concomitant therapy is the best regimen for the first-line H. pylori eradication showing consistently higher eradication rate with an increasing trend for the last 10 years in Korea. Bismuth quadruple therapy should be considered for second-line therapy after eradication failure using non-bismuth quadruple therapy.

Comparison of the Efficacy of Polaprezinc Plus Proton Pump Inhibitor and Rebamipide Plus Proton Pump Inhibitor Treatments for Endoscopic Submucosal Dissection-induced Ulcers.

GOALS: We assessed the efficacy of polaprezinc plus proton pump inhibitor (PPI) treatment for endoscopic submucosal dissection (ESD)-induced ulcer healing compared with rebamipide plus PPI treatment. BACKGROUND: ESD has been widely used as a local treatment option that cures gastric neoplasms. However, it causes large and deep artificial ulcers, and there are no guidelines with regard to the optimal treatment durations and drug regimens for ESD-induced ulcers. Polaprezinc is effective for promoting ulcer healing and helps enhance the quality of ulcer healing. STUDY: Two hundred ten patients with ESD-induced ulcers were randomly allocated to treatment with polaprezinc (150 mg/d) plus pantoprazole (40 mg/d) or treatment with rebamipide (300 mg/d) plus pantoprazole (40 mg/d). We evaluated the ulcer healing rate and condition of the ulcer at 4 weeks after dissection. The χ2 or Fisher exact test and the Student t test were used. RESULTS: The ulcer healing rates at 4 weeks after dissection in the polaprezinc plus pantoprazole treatment group were not inferior compared with those in the rebamipide plus pantoprazole treatment group, both in the intention-to-treat analysis (90.3% and 91.4%, respectively, P=0.523) and per-protocol analysis (89.9% and 91.1%, respectively, P=0.531). The short procedure time was an independent predictive factor for a high ulcer healing rate (odds ratio: 0.975; 95% confidence interval: 0.958-0.993; P=0.006). CONCLUSION: The polaprezinc plus PPI treatment showed noninferiority to rebamipide plus PPI treatment in the ulcer healing rate at 4 weeks after ESD.

Clinical outcomes of endoscopic resection for undifferentiated intramucosal early gastric cancer larger than 2 cm.

BACKGROUND: This study investigated the long-term clinical outcomes of endoscopic resection (ER) for undifferentiated-type (UD) early gastric cancer (EGC), with tumor size > 2 cm as the only non-curative factor. METHODS: From among 1123 patients who underwent ER for UD EGC at 18 tertiary hospitals in Korea between 2005 and 2014, we identified 216 patients with UD intramucosal EGC > 2 cm, which was completely resected, with negative resection margins, and absence of ulceration and lymphovascular invasion. The patients were divided into the additional surgery (n = 40) or observation (n = 176) groups, according to post-ER management and were followed up for a median duration of 59 months for recurrence and 90 months for overall survival. RESULTS: Lymph node (LN) or distant metastasis or cancer-related mortality was not observed in the surgery group. In the observation group, two (1.1%) patients developed LN or distant metastasis with a 5-year cumulative risk of 0.7%, and one (0.6%) patient died of gastric cancer. The 5- and 8-year overall survival rates were 94.1% and 89.9%, respectively, in the observation group and 100.0% and 95.2%, respectively, in the surgery group (log-rank P = 0.159). Cox regression analysis did not reveal an association between the observation group and increased mortality. CONCLUSION: The risk of LN or distant metastasis was not negligible, but as low as 1% for patients undergoing non-curative ER for UD EGC, with tumor size > 2 cm as the only non-curative factor. Close observation may be an alternative to surgery, especially for older patients or those with poor physical status.

Comparison between endoscopic submucosal resection and surgery for the curative resection of undifferentiated-type early gastric cancer within expanded indications: a nationwide multi-center study.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) for undifferentiated early gastric cancer (UD EGC) has debate due to the risk of lymph node metastasis. We investigated the outcomes of ESD compared to those of surgery for the UD EGC within expanded indication. METHODS: We reviewed 971 UD EGC patients performed ESD across 18 hospitals in Korea and 1812 patients who underwent surgical resection in two hospitals between February 2005 and May 2015. Of these cases, we enrolled a curative resected ESD group of 328 patients and surgery group of 383 cases within an expanded indication. Overall outcomes and one-to-one propensity score-matched (218 ESD group vs 218 surgery group cases) outcomes for these two groups were analyzed. RESULTS: Over the 75.6 month median follow-up period for the 711 enrolled cases, recurrences occurred in 22 patients (6.7%) in the ESD group but not in the surgery group. Overall survival (OS) was higher in the surgery group (p = 0.0316) in all cases, but there was no significant difference after propensity score matching (p = 0.069). According to the histologic type in propensity score matching, the OS of signet ring cell carcinoma and poorly differentiated carcinoma patients did not differ between the ESD and surgery groups (p = 0.1189 and p = 0.3087, respectively). In the surgery group involving expanded criteria, lymph node metastasis was found in six cases (1.56%). CONCLUSIONS: Although ESD shows comparable outcomes to surgery for the UD EGC within expanded indications, appropriate patient selection is needed for the ESD due to the possibility of lymph node metastasis.

Risk factors of lymph node metastasis after non-curative endoscopic resection of undifferentiated-type early gastric cancer.

BACKGROUND: This study aimed to investigate risk factors for lymph node (LN) or distant metastasis after non-curative endoscopic resection (ER) of undifferentiated-type early gastric cancer (EGC). METHODS: Of 1124 patients who underwent ER for undifferentiated-type gastric cancer at 18 tertiary hospitals across six geographic areas in Korea between 2005 and 2014, 634 with non-curative ER beyond the expanded criteria were retrospectively enrolled. According to the treatment after ER, patients were divided into additional surgery (n = 270) and follow-up (n = 364) groups. The median follow-up duration was 59 months for recurrence and 84 months for mortality. RESULTS: LN metastasis was found in 6.7% (18/270) of patients at surgery. Ulcer [odds ratio (OR) 3.83; 95% confidence interval (CI) 1.21-12.13; p = 0.022] and submucosal invasion (OR 10.35; 95% CI 1.35-79.48; p = 0.025) were independent risk factors. In the follow-up group, seven patients (1.9%) developed LN or distant recurrence. Ulcer [hazard ratio (HR) 7.60; 95% CI 1.39-35.74; p = 0.018], LVI (HR 6.80; 95% CI 1.07-42.99; p = 0.042), and positive vertical margin (HR 6.71; 95% CI 1.28-35.19; p = 0.024) were independent risk factors. In the overall cohort, LN metastasis rates were 9.6% in patients with two or more risk factors and 1.2% in those with no or one risk factor. CONCLUSIONS: LVI, ulcer, submucosal invasion, and positive vertical margin are independently associated with LN or distant metastasis after non-curative ER of undifferentiated-type EGC. Surgical resection is strongly recommended for patients with two or more risk factors.

Establishing Machine Learning Models to Predict Curative Resection in Early Gastric Cancer with Undifferentiated Histology: Development and Usability Study.

BACKGROUND: Undifferentiated type of early gastric cancer (U-EGC) is included among the expanded indications of endoscopic submucosal dissection (ESD); however, the rate of curative resection remains unsatisfactory. Endoscopists predict the probability of curative resection by considering the size and shape of the lesion and whether ulcers are present or not. The location of the lesion, indicating the likely technical difficulty, is also considered. OBJECTIVE: The aim of this study was to establish machine learning (ML) models to better predict the possibility of curative resection in U-EGC prior to ESD. METHODS: A nationwide cohort of 2703 U-EGCs treated by ESD or surgery were adopted for the training and internal validation cohorts. Separately, an independent data set of the Korean ESD registry (n=275) and an Asan medical center data set (n=127) treated by ESD were chosen for external validation. Eighteen ML classifiers were selected to establish prediction models of curative resection with the following variables: age; sex; location, size, and shape of the lesion; and whether ulcers were present or not. RESULTS: Among the 18 models, the extreme gradient boosting classifier showed the best performance (internal validation accuracy 93.4%, 95% CI 90.4%-96.4%; precision 92.6%, 95% CI 89.5%-95.7%; recall 99.0%, 95% CI 97.8%-99.9%; and F1 score 95.7%, 95% CI 93.3%-98.1%). Attempts at external validation showed substantial accuracy (first external validation 81.5%, 95% CI 76.9%-86.1% and second external validation 89.8%, 95% CI 84.5%-95.1%). Lesion size was the most important feature in each explainable artificial intelligence analysis. CONCLUSIONS: We established an ML model capable of accurately predicting the curative resection of U-EGC before ESD by considering the morphological and ecological characteristics of the lesions.

Association between the National Cancer Screening Programme (NSCP) for gastric cancer and oesophageal cancer mortality.

BACKGROUND: The aim was to evaluate whether this gastric cancer-screening programme was effective in reducing oesophageal cancer mortality. METHODS: A population-based retrospective cohort study was conducted using the Korean National Cancer Screening Programme (NCSP) database. The study cohort comprised 16,969 oesophageal cancer patients who had been diagnosed in 2007-2014. We analysed the association between the history of NSCP for gastric cancer and oesophageal cancer mortality. RESULTS: Compared with never-screened subjects, ever-screened subjects had an overall HR for oesophageal cancer mortality of 0.647 (95% CI, 0.617-0.679). According to the time interval since screening, the HRs of death were 0.731 (95% CI, 0.667-0.801) for 6-11 months, 0.635 (95% CI, 0.594-0.679) for 12-23 months, 0.564 (95% CI, 0.522-0.610) for 24-35 months and 0.742 (95% CI, 0.679-0.810) for ≥36 months. According to the last screening modality, the HRs of death were 0.497 (95% CI, 0.464-0.531) for upper endoscopy, and 0.792 (95% CI, 0.749-0.838) for UGIS. Upper endoscopy reduced the mortality consistently in all age groups over 50 years, whereas UGIS could not. CONCLUSION: The NCSP for gastric cancer was effective in reducing the mortality of oesophageal cancer, and upper endoscopy was superior to UGIS.

Correction: Association between the National Cancer Screening Programme (NSCP) for gastric cancer and oesophageal cancer mortality.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Stratification of Postsurgical Computed Tomography Surveillance Based on the Extragastric Recurrence of Early Gastric Cancer.

OBJECTIVE: To stratify the postsurgical computed tomography (CT) surveillance based on a risk-scoring system for predicting extragastric recurrence after surgical resection of early gastric cancer (EGC). SUMMARY OF BACKGROUND DATA: Postsurgical CT surveillance should not be routinely performed in all patients because of the low incidence of extragastric recurrence and potential risk of radiation exposure. METHODS: Data from 3162 patients who underwent surgical resection for EGC were reviewed to develop a risk-scoring system to predict extragastric recurrence. Risk scores were based on the predictive factors for extragastric recurrence, which were determined using Cox proportional hazard regression model. The risk-scoring system was validated by Uno censoring adjusted C-index. External validation was performed using an independent dataset (n = 430). RESULTS: The overall incidence of extragastric recurrence was 1.4% (44/3162). Five risk factors (lymph node metastasis, indications for endoscopic resection, male sex, positive lymphovascular invasion, and elevated macroscopic type), which were significantly associated with extragastric recurrence, were incorporated into the risk-scoring system, and the patients were categorized into 2 risk groups. The 10-year extragastric recurrence-free survival differed significantly between low- and high-risk groups (99.7% vs 96.5%; P < 0.001). The predictive accuracy of the risk-scoring system in the development cohort was 0.870 [Uno C-index; 95% confidence interval (95% CI), 0.800-0.939]. Discrimination was good after internal (0.859) and external validation (0.782, 0.549-1.000). CONCLUSION: This risk-scoring system might be useful to predict extragastric recurrence of EGC after curative surgical resection. We suggest that postsurgical CT surveillance to detect extragastric recurrence should be avoided in the low-risk group.

The Suggestion of Revised Criteria for Endoscopic Resection of Differentiated-Type Submucosal Gastric Cancer.

BACKGROUND: Early gastric cancer that meets the expanded criteria for endoscopic resection (ER) is expected to be associated with a negligible risk for lymph node metastasis (LNM); however, recent studies have reported LNM in submucosal gastric cancer patients who met the existing criteria. In this study, we develop the revised criteria for ER of submucosal gastric cancer with the aim of minimizing LNM. METHODS: We analyzed the clinicopathological data of 2461 patients diagnosed with differentiated, submucosal gastric cancer who underwent surgery at three tertiary hospitals between March 2001 and December 2012, and re-analyzed the pathological slides of all patients. The depth of submucosal invasion was measured histopathologically in two different ways (the classic and alternative methods) to obtain accurate data. RESULTS: Of the enrolled subjects, 306 (17.0%) had LNM. The width of submucosal invasion correlated well with the LNM. We defined the depth and width of submucosal infiltration associated with the lowest incidence of LNM. None of the 254 subjects developed LNM when the following criteria were met: tumor diameter ≤ 3 cm, submucosal invasion depth < 1000 µm (as measured using the alternative method), submucosal invasion width < 4 mm, no lymphovascular invasion, and no perineural invasion; however, LNM was observed in 2.7% of subjects (6/218) who met the existing criteria. CONCLUSIONS: We revised the criteria for ER by adopting the alternative method to measure the depth of submucosal invasion and adding the width of such invasion. Our criteria better predicted LNM than the current criteria used to select ER to treat submucosal gastric cancer.

Effect of histologic differences between biopsy and final resection on treatment outcomes in early gastric cancer.

BACKGROUND AND STUDY AIMS: Biopsy-based histologic diagnosis is important in determining the treatment strategy for early gastric cancer (EGC). However, there are few studies on how histologic discrepancy may affect patients' treatment outcomes. We aimed to investigate the impact of histopathologic differences between biopsy and final specimens from endoscopic resection (ER) or gastrectomy on treatment outcomes in patients with EGC. We also examined the predictive factors of histologic discrepancy. PATIENTS AND METHODS: We analyzed the data of 1851 patients with EGC treated with ER or gastrectomy. We compared the histology between biopsies and final resected specimens from ER or gastrectomy. We also examined changes in treatment outcomes according to histologic differences. RESULTS: Histologic discrepancy was observed in 11.9% of patients in the ER group and 10.7% of those in the gastrectomy group. In patients treated with ER who showed histologic discrepancy, 80.9% showed differentiated-type EGC (D-EGC) on biopsy but undifferentiated-type-EGC (UD-EGC) after ER, of which 78.9% were non-curative resection. In patients treated with gastrectomy who showed histologic discrepancy, 39% showed UD-EGC on biopsy but showed D-EGC after gastrectomy. A total of these patients had absolute and expanded indications for ER. Moderately differentiated and poorly differentiated adenocarcinoma on biopsy were predictive factors of histologic discrepancy in UD-EGC and D-EGC on final resection, respectively. CONCLUSIONS: About 10% of patients showed histologic discrepancy between biopsy and final resection with ER or gastrectomy. Histologic discrepancy can affect treatment outcomes, such as non-curative resection in ER or missing the opportunity for ER in gastrectomy.

Features of Postcolonoscopy Colorectal Cancer and Survival Times of Patients in Korea.

The literature reporting survival times after diagnosis of postcolonoscopy colorectal cancer (PCCRC) is inconsistent1-4 and few data are available from Asian countries. Asian countries have different health care utilization patterns and resources from those of Western countries, and the characteristics and survival of PCCRC patients may be different. This study aimed to compare the features and survival times of PCCRC patients with those of detected CRC patients in Korea.

HER2 Regulates Cancer Stem Cell Activities via the Wnt Signaling Pathway in Gastric Cancer Cells.

INTRODUCTION: Human epidermal growth factor 2 (HER2) gene overexpression in breast carcinoma cell lines has been shown to drive mammary carcinogenesis and tumor growth and invasion through its effects on mammary stem cells. OBJECTIVE: Therefore, we investigated the mechanism by which HER2 regulates cancer stem cell (CSC) activity in gastric cancer cells. METHODS: HER2 was transfected into MKN28 gastric cancer cells, and its role in regulating CSC activity was determined by characterizing the HER2-overexpressing cells. RESULTS: The sphere formation assay revealed that the sphere sizes and frequency of sphere formation were significantly greater for the HER2-overexpressing cells than for the MKN28 control cells. The CSC markers Oct-4 and BMI1 were more highly expressed in the HER2-overexpressing cells, as were the EMT markers. This was accompanied by a significant enhancement in cellular invasion of the Matrigel and migration. The E-cadherin level was significantly downregulated, and the mesenchymal marker Snail upregulated, in the HER2-transfected cells. HER2 overexpression activated the well-characterized CSC-associated Wnt/ß-catenin signaling pathway, as shown by the luciferase assay. After treatment of these cells with the Wnt signal inhibitor PRI-724, the BMI1 and Oct-4 levels were decreased for 24 h and Snail was also downregulated. Immunofluorescence staining revealed the significant restoration of E-cadherin levels in the HER2-transfected cells after PRI-724 treatment. CONCLUSIONS: These results established a role for HER2 in regulating gastric CSC activity, with Wnt/ß-catenin signaling being mediated via a HER2-dependent pathway. In summary, HER2-overexpressing gastric cancer cells exhibited increased stemness and invasiveness and were regulated by Wnt/ß-catenin signaling.

Gentamicin-intercalated smectite as a new therapeutic option for Helicobacter pylori eradication.

Objectives: Novel antibacterial strategies against Helicobacter pylori are needed because H. pylori strains are acquiring resistance to antibiotics. We evaluated the efficacy of gentamicin-intercalated smectite hybrid (S-GEN)-based treatment regimens in a murine model of H. pylori infection. Methods: Two groups of 10 rats were administered either smectite or S-GEN to measure coverage of the gastric mucosa. To evaluate anti-H. pylori efficacy, mice were divided into eight groups of 10 mice each given different treatments, and H. pylori eradication was assessed by a Campylobacter-like organism (CLO) test and H. pylori PCR of the gastric mucosa, and H. pylori antigen and H. pylori PCR analysis of mouse faeces. The levels of proinflammatory cytokines were examined. Results: S-GEN was retained in the gastric mucosal layer with a >60% distribution ratio for up to 1 h, and the S-GEN-based triple regimen decreased bacterial burden in vivo compared with that of untreated mice or mice treated with other regimens. The cure rates in the CLO test and H. pylori PCR from gastric mucosa were 70%, 60%, 80%, 50%, 60% and 60% in Groups III-VIII, respectively. Those for H. pylori PCR in the faeces of mice were 90% and 100% in Group III with standard therapy and Group V with triple therapy including S-GEN, respectively. S-GEN triple therapy also reduced the levels of proinflammatory cytokines. Conclusions: These results suggest that S-GEN is a promising and effective therapeutic agent for the treatment of H. pylori infection.